tbuckley/cabot-search huggingface dataset:
Local recurrence after curative resection of early gastric cancer by endoscopic submucosal dissection.
Authors: Moon Kyung Joo, Jong-Jae Park, Beom Jae Lee, Sunsuk Kim, Hoon Jai Chun
Journal: Journal of Clinical Oncology (2023)

388 Background: We investigate the local recurrence rate and its risk factors among patients who underwent endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) and are judged as curative resection. Methods: We enrolled patients who were diagnosed as EGC and underwent ESD during 2006 and 2020. Local recurrence after ESD was confirmed by histopathologic evaluation by endoscopic biopsy at ESD site during endoscopic surveillance. Results: A total of 936 patients underwent ESD for EGC, achieved curative resection and were followed up more than 12 months. Among them, 14 cases of local recurrence were found (14/936, 1.5%) during 53.2 months of follow-up. Compared with patients without local recurrence, those with local recurrence showed male-predominance (677/922 vs. 14/14, P=0.025), frequent presence of synchronous tumor (123/922 vs. 6/14, P=0.001) and larger tumor size (16.3 vs. 26.3 mm, P=0.001). Kaplan-Meier graph also showed that local recurrence significantly occurred in subgroup with male, presence of synchronous tumor and tumor size ≥ 20 mm ( P=0.028, 0.009 and &lt;0.001 by log rank test, respectively). After propensity score matching for gender, age and comorbidities with 1:5 ratio, tumor size ≥ 20 mm was the only significant factor for local recurrence (odds ratio: 3.886, 95% confidence interval: 1.012-14.922, P=0.048) Conclusions: Endoscopists need to be cautious for local recurrence at ESD site even after curative resection of EGC, especially for large tumor size.
Disparities in colorectal cancer: Trends of reduced screening among minority populations.
Authors: Ahmed Ouni, Kristin Cardiel Nunez, Aneesah Garrett, Michael Heckman, Bhaumik Brahmbhatt, Timothy A A Woodward
Journal: Journal of Clinical Oncology (2023)

18 Background: Studies have shown that African Americans (AA) are at increased risk for Colorectal Cancer (CRC) compared to other groups. Despite advancements in CRC screening modalities, few studies have investigated disparities in CRC screening among this vulnerable population. Methods: We performed a retrospective review of patients of age 45 or older who were seen in Family Medicine (FM), Internal Medicine (IM), or Gastroenterology (GI) between January 1, 2015 and December 31, 2021 at the Mayo Clinic. Information was collected regarding patient characteristics (age, sex, Charlson comorbidity score, race), and outcomes (whether a Cologuard test was ordered on the same day as the initial appointment, and whether the patient underwent a colonoscopy within 1 year after the initial appointment). Categorical variables were summarized with number and percentage of patients. Outcomes were compared between race groups (Caucasian, AA, Asian, Other) using unadjusted and multivariable logistic regression models. Multivariable models were adjusted for age, sex, and Charlson comorbidity score. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. P-values &lt;0.05 were considered as statistically significant, and all statistical tests were two-sided. Results: Overall, 558,078 were included for analysis and 14,607 (2.6%) were AA. Overall, AA patients for less likely to have Cologuard ordered compared to Caucasians (OR=0.62, p&lt;0.001), notably driven by patient seen in the FM group (OR=0.54, p&lt;0.001) and no statistically significant difference was observed in the IM and GI groups (p=0.055 and p=0.43, respectively). Notably, compared to Caucasian patients, Asian patients were overall more likely to have Cologuard ordered (OR=1.23, p=0.003). In multivariable analysis assessing the likelihood of having a colonoscopy performed within 1 year of the initial appointment, the likelihood of a colonoscopy within 1 year of initial clinic visit was significantly lower for AA compared to Caucasian patients (OR=0.50, p=0.028). This difference was strongest in FM patients (OR=0.26, p=0.022) and was not significant for IM (OR=0.67, p=0.37) or GI (OR=2.31, p=0.25). Conclusions: In this study, we found that AA ethnicity is associated with reduced likelihood of having Cologuard ordered compared to Caucasian patients. Furthermore, AA patients were less likely to have colonoscopy ordered within 1 year of initial visit clinic visit among the overall cohort, highlighting important disparities in CRC screening among this vulnerable patient population notably for those seen in the FM group. Future studies are needed to assess other barriers for CRC screening in this population.
Assessment of complete pathologic response after neoadjuvant immunotherapy for MSI-H gastrointestinal cancers.
Authors: Kruti Bhagirath Vora, Ben Ouyang, Leon Pappas, Kerry Lynn Reynolds, Matthew Strickland, Jill N. Allen, Colin D. Weekes, Ryan Bruce Corcoran, Lawrence Scott Blaszkowsky, David P. Ryan, Joseph Wang Franses, Sakti Chakrabarti, Samuel J Klempner, Aparna Raj Parikh
Journal: Journal of Clinical Oncology (2023)

43 Background: Immunotherapy (IO) has shown remarkable efficacy in gastrointestinal (GI) cancers with high microsatellite instability (MSI-H). We evaluated real world outcomes of patients treated with neoadjuvant IO for MSI-H colorectal (CRC) and gastroesophageal (GE) cancers. Methods: We queried diagnoses, pathology reports, and clinic notes of patients receiving IO at Massachusetts General Hospital from October 2014 to March 2022 using the Research Patient Data Registry and MATLAB. 1140 patients were identified with esophageal, gastric, colon, or rectal primaries. Of these, 56 were MSI-H and seven received neoadjuvant IO with curative intent. Results: Of the seven patients who received neoadjuvant IO for MSI-H CRC or GE cancers, three patients achieved complete pathologic response (pCR). Three patients had partial responses; one had a single residual lymph node tumor cell, one had residual T1b tumor and negative nodes, and one had residual T3 tumor and positive nodes. All patients with pCR had non-metastatic disease. Three of four patients with partial responses or progression had metastatic disease. Five patients had no recurrence by median follow-up of 10 months post-resection. One patient's cancer recurred 15 months post-resection, and one patient had progressive disease on neoadjuvant IO so did not undergo primary resection. Conclusions: Neoadjuvant IO shows promise for MSI-H GI cancers. Three of seven patients (43%) had pCR and three others (43%) had notable partial responses. There is a need to understand IO-refractory primary tumors and the differing effects of IO in local versus metastatic disease. While our data is limited by sample size, larger clinical trials can establish the safety and utility of neoadjuvant IO, potentially sparing many patients from surgery. We will collaborate with other centers for a larger scale analysis on neoadjuvant IO in MSI-H GI cancers. [Table: see text]
Esophagogastrostomy with fundoplication versus double-tract reconstruction after laparoscopic proximal gastrectomy for gastric cancer.
Authors: Shinta Tominaga, Toshiyasu Ojima, Keiji Hayata, Junya Kitadani, Hiroki Yamaue, Manabu Kawai
Journal: Journal of Clinical Oncology (2023)

346 Background: Upper-third gastric cancer has been increasing in incidence worldwide and performance of laparoscopic proximal gastrectomy has become increasing common. Various reconstructive procedures after laparoscopic proximal gastrectomy have been reported, but the optimal reconstructive procedure is unclear. Methods: This single-center retrospective study included 53 consecutive patients with early gastric cancer in the upper third of the stomach who received laparoscopic proximal gastrectomy at our hospital between September 2013 and November 2019. Of these 53 patients, 39 underwent esophagogastrostomy with fundoplication. In the 14 patients requiring resection of the abdominal esophagus or where the size of the remnant stomach was 50% or less, we performed double-tract reconstruction. We compared the surgical and nutritional outcomes of patients who underwent esophagogastrostomy or double-tract reconstruction after laparoscopic proximal gastrectomy. Results: There was no significant difference between the two groups regarding blood loss, incidence of postoperative complications, occurrence of gastroesophageal reflux disease, food intake, reflux symptoms, or usage of proton pump inhibitors. There was no significant difference in the rate of body weight change at 6 or 12 months, or in biochemical markers (hemoglobin, total protein and albumin) at 12 months. However, eight patients (21%) in the esophagogastrostomy group had extreme body weight loss (≥20%) within 12 months. Conversely, in the double-tract reconstruction group, no patients had any extreme body weight loss ( P = 0.013). Conclusions: Double-tract reconstruction is useful after laparoscopic proximal gastrectomy, especially in terms of preventing extreme body weight loss.
Efficacy of pembrolizumab as first-line therapy in patients with mismatch repair–deficient metastatic colorectal cancer in relation to the metastatic site.
Authors: Bahar Saberzadeh Ardestani, Jeremy Clifton Jones, Joleen M. Hubbard, Robert R. McWilliams, Thorvardur Ragnar Halfdanarson, Qian Shi, Bassam Bassam Sonbol, Jonathan Ticku, Zhaohui Jin, Frank A. Sinicrope
Journal: Journal of Clinical Oncology (2023)

57 Background: Metastatic colorectal cancer (mCRC) with deficient DNA mismatch repair (dMMR) or microsatellite instability-high (MSI-H) show frequent and durable responses to programmed cell death -1 (PD-1) blockade. While the majority of these tumors are sporadics and observed in elderly patients, first-line data are limited to the KEYNOTE-177 study. Here, we report a consecutive series of elderly patients with dMMR mCRC treated with pembrolizumab in routine clinical practice that includes analysis of clinical outcome based on metastatic site. Methods: Patients with dMMR mCRC received first-line pembrolizumab (200 mg every 3 weeks) (N = 41) at Mayo Clinic and Mayo Clinic Health System (2015-2022). Clinicopathological features including metastatic site and molecular data ( BRAF V600E , KRAS) were analyzed in relationship to tumor response rate (RECIST version 1.1). Furthermore, these variables were also analyzed in relationship to patient progression-free survival (PFS) using Kaplan-Meier methodology and multivariable stepwise Cox regression. Results: Among patients with dMMR mCRC, 29/41 (70.7%) were female, 30 (78.9%) harbored BRAF V600E , and 32 (80%) were sporadic. Median age at start of treatment was 80.6 years (IQR of 75.9, 85.9) and median number of treatment cycles was 9 (IQR: 4, 20). At a median follow-up of 23 months (range, 3.0 to 88.5), patient median PFS was 21.3 months (95% CI: 6.4, 38.5). An overall response was observed in 48.8% (20 of 41) of patients including 13 (31.7%) complete (CR) and 7 (17.1%) partial responses (PR). The median duration of response was 42.2 months (95%CI: 8.6, NR). Patients with metastases that included liver had significantly poorer PFS compared to those with non-liver metastases (HR adj 3.40 (95%CI: 1.27-9.13); P adj = 0. 01). In this regard, responses (CR, PR) to pembrolizumab were observed in 3 (21.4%) patients with liver metastasis compared to 17 (62.9%) of those with non-liver metastases. Treatment-related grade 3 or 4 adverse events were observed in 9 (22.0%) patients of whom two discontinued therapy, and there was one treatment-related death. Conclusions: First-line therapy with pembrolizumab for dMMR mCRC significantly prolonged survival in an elderly patient population with manageable toxicity in routine clinical practice. Moreover, the survival benefit of pembrolizumab was significantly attenuated in patients with liver vs non-liver metastases.
The Endoscopic Ultrasound Molecular Analysis of Pancreatic Cancer (EUMEPC) study.
Authors: Joanne Lundy, Hugh Gao, Trevor Wilson, Owen McKay, Andrew Perry, Vikki M Marshall, Daniel Croagh
Journal: Journal of Clinical Oncology (2023)

751 Background: Pancreatic cancer carries a dismal prognosis and limited treatment options. Attempts to implement precision therapies have proved difficult to date, in part due to challenges obtaining high quality genetic material from pancreatic biopsies. Endoscopic ultrasound (EUS) is a common diagnostic procedure, but limited data is available on the clinical utility of these biopsies for comprehensive molecular profiling (CMP) to inform therapeutic choices. Methods: This study aimed to enrol up to 150 patients undergoing EUS biopsies for pancreatic cancer, in order to complete targeted DNA/RNA sequencing on 100. The primary outcome was to characterise the proportion of patients able to undergo CMP on their diagnostic EUS biopsies, with fresh-frozen biopsies preferred but FFPE specimens accepted if there was no alternative. Secondary endpoints included the proportion of patients with clinically relevant molecular findings as determined by Molecular Tumour Board (MTB) discussion, proportion of patients initiating targeted therapies, and quantitative/qualitative analysis on molecular material derived from fresh-frozen versus FFPE EUS biopsies. Results: 109 patients have been enrolled since May 2020, and molecular profiling has been completed for 102 patients. 2 patients (1.8%) were excluded due to having no available biopsies, and 5 biopsies (4.7%) were unable to be sequenced due to inadequate quality metrics. Common oncogenes were detected at roughly expected frequencies, with mutations in KRAS occurring in 91 (89.2%), TP53 in 67 (65.7%), SMAD4 in 11 (10.8%) and CDKN2A in 7 (6.8%). Median tumour mutation burden (TMB) in this cohort was low at 3.1Mut/Mb although 7 patients (6.9%) had a high TMB (defined as &gt;10Mut/Mb), of which 3 (2.9%) had markedly hypermutated tumours (&gt;200Mut/Mb). All processed samples were microsatellite stable. Therapeutically relevant mutations were detected in 21 (20.6%) including RNF43 in 7 patients (6.9%), KRAS G12C and BRCA in 3 patients each (2.9%), in addition to BRAF V600E in 2 (1.9%), and CHEK2 and BARD1 mutations in 1 each (0.9%). High TMB was observed in 7 patients (6.9%). To date, 5 patients (4.9%) have commenced on targeted therapies, with one patient notably experiencing a complete response to targeted therapy which has now been sustained for &gt;12 months. Conclusions: This real-world study confirms the utility of endoscopic biopsies as a valuable and reliable source of genetic material for clinically relevant molecular tumour profiling. Secondary analyses are underway to further characterise treatment and survival implications in this cohort.
Clinical performance of a multimodal screening blood test for advanced adenomas and CRC in an average-risk cohort of 1,038 participants.
Authors: Shai Friedland, Drew Watson, Douglas K. Rex, Ashish Nimgaonkar, Zhen Zhang, Alex Atkins, Ben Hsieh, Jr-Ming Lai, Stephen Su, Jen-chia Wu, Hung-Jen Shao, Jessica Tesoriero, Lindsey Hannah, John McGowan, Samir Gupta, John J. Sninsky, Rui Mei
Journal: Journal of Clinical Oncology (2023)

75 Background: The National Polyp Study and 2021 USPSTF CRC-update highlight that the detection and removal of precancerous advanced adenomas (AA) prevents colorectal cancer (CRC), decreases mortality, and leads to higher cost savings than early cancer detection. Performance of a multimodal blood-based test for the detection of CRC and AA that integrates sensitive and accurate detection of circulating gastrointestinal epithelial cells and somatic oncologic variants as well as SEER data of the impact of sex and age is described. Methods: The prospective study included average-risk, asymptomatic screening subjects from 18 geographically dispersed US colonoscopy centers with blood drawn before colonoscopy. Monte Carlo cross-validation (MCCV) methods were used to evaluate the robustness of test performance through 2000 iterations of independent training and validation using bootstrap resampling with stratification to balance patient histopathology, age, and gender. Results include point estimates, confidence intervals, and distributions of sensitivity and specificity to detect AA and CRC. Results: The study cohort (53.2% female; mean age 56.7 yrs.) consisted of 1,038 subjects (White 65.1%; Black 8.5%; Hispanic 24.8%; Asian 1.7%); of which 954 (92%) were asymptomatic, average-risk screening subjects without age enrichment (including 11 CRC and 93 AA) and 84 (8%) were enriched case-control (65 CRC and 19 AA) subjects. The algorithm derives a test score from 0 (low risk) to 100 (high risk) as a quantitative measure of AA and CRC risk. A pre-defined cut point of 47.2 yields a test specificity &gt; 90%, and 92.1% and 54.5% sensitivity for the detection of CRC and AA, respectively. Estimated sensitivities and selected Clopper-Pearson (Exact) 95% confidence intervals based on validation results from MCCV are presented. A split analysis shows for the 954 intended-use, asymptomatic, average-risk screening subjects, the sensitivity for CRC and AA are 100% and 55.9%. Conclusions: A multi-site, prospective, average-risk CRC screening study using a multimodal assay had high sensitivity and specificity for AA and CRC. The quantitative correlation of test scores with disease pathology indicates that the modes of the assay interrogate the primary underlying pathophysiology of disease. The results demonstrate the potential of this novel test to meet the clinically unmet need for a noninvasive strategy for CRC screening and prevention that detects CRC and AA. Clinical trial information: NCT05127096 . [Table: see text]
Adjuvant chemotherapy for older patients with stage II/III gastric cancer: A retrospective cohort study.
Authors: Yu-Hsuan Shih, Hsin-Chen Lin, Chiann-Yi Hsu
Journal: Journal of Clinical Oncology (2023)

303 Background: Current clinical guidelines recommended adjuvant chemotherapy for stage II and stage III gastric cancer after operation. The older patients were underrepresented in clinical trials and the role of adjuvant chemotherapy for older patients is unclear. We aimed to investigate the benefit of adjuvant chemotherapy in older patients with stage II and stage III gastric cancer. Methods: We retrospectively reviewed the medical records of patients with stage II-III gastric adenocarcinoma and underwent curative surgery at Taichung Veterans General Hospital (Taichung, Taiwan) between January 2009 and June 2017. The clinical characteristics and outcomes of patients ≥70-year-old were compared between patients received adjuvant chemotherapy or not received adjuvant chemotherapy. Results: A total of 357 patients were analyzed and 164 patients were older or equal to 70 years old. Majority of the young patients received adjuvant chemotherapy but only two-thirds of the old patients received adjuvant chemotherapy (93.8% vs. 61%; P&lt;0.001). Among older patients, receipt of adjuvant chemotherapy was associated with longer disease-free survival (DFS) (10-year DFS, 45.89% vs. 17.55%; P&lt;0.001) and overall survival (OS) (10-year OS, 61.71% vs. 36.27%; P=0.023) compared with patients who did not receive adjuvant chemotherapy. The total gastrectomy (hazard ratio (HR): 2.26; P=0.015), more advanced stage (HR: 2.71; P=0.018), positive surgical margin (HR: 2.56; P=0.02), elevated baseline carcinoembryonic antigen (HR: 2.37; P=0.026) were independent prognostic factors for OS in patients ≥70-year-old. Notably, the benefit adjuvant chemotherapy in older patients was significant in univariate analysis (HR: 0.53; P=0.025) but was not confirmed in multivariate analysis (HR: 0.52; P=0.072). Conclusions: The benefit of adjuvant chemotherapy in older patients with stage II-III gastric cancer was controversial in this retrospective study. Further prospective studies are needed to investigate this issue.
Metabolomic differences in young-onset versus average-onset colorectal adenocarcinoma.
Authors: Thejus Jayakrishnan, Nicole Farha, Arshiya Mariam, Daniel Miller Rotroff, Federico Aucejo, Shimoli V Barot, Madison Conces, Kanika G. Nair, Smitha S. Krishnamurthi, Stephanie Schmit, David Liska, Alok A. Khorana, Suneel Deepak Kamath
Journal: Journal of Clinical Oncology (2023)

174 Background: Novel deleterious effects of environmental exposures may play a role in the rising incidence of young-onset colorectal cancer (yoCRC). We used metabolomics to assess differences between yoCRC and average-onset CRC (aoCRC), in comparison to healthy controls, which may suggest certain exposure risks. Methods: Patients with stage I-IV CRC and healthy controls were identified from prospective biobanks and categorized based on age&lt;50 years (yoCRC or young controls) or age&gt;60 years (aoCRC or older controls). Serum metabolites were profiled using GC-TOF mass spectrometry. Differential abundance of metabolites was investigated using unadjusted logistic regression. Metabolic pathway analysis was performed using Metaboanalyst 5.0. All p-values were adjusted for multiple testing (false-discovery rate, FDR p&lt;0.20 considered significant). Results: The study population comprised 170 CRC patients (66 yoCRC and 104 aoCRC) and 49 healthy controls (34 young and 15 old). Association analyses revealed four differentially abundant metabolites: citrate (FDR p=0.04), cholesterol (0.14), and two unidentified metabolites (UM). Metabolic pathways significantly altered in yoCRC vs. aoCRC included: carbohydrate metabolism (citrate cycle, FDR p=0.11), carbohydrate biosynthesis (glyoxylate and dicarboxylate metabolism, FDR p=0.03), amino-acid metabolism (alanine, aspartate, and glutamate metabolism, FDR p=0.04, arginine biosynthesis, FDR p=0.04, and amino-acid t-RNA biosynthesis, FDR p=0.04). There were no significant metabolomic differences between young and older controls. Conclusions: We identified significant differences in the citrate cycle - a core pathway of cellular metabolism and associated with colorectal cancer. Metabolomic differences in pathways of carcinogenic significance (aspartate) and environmental exposures (arginine and dietary red meat) were also noted, suggesting potential relationships with younger age of CRC onset. The study provides future directions for more precise analyses with a larger sample size for healthy controls and adjusting for confounders. [Table: see text]